The central theme of this proposal is the role of extracellular matrix macromolecules in cell behavior and tissue morphogenesis in the embryonic limb, and the regulation of synthesis, assembly and degradation of these macromolecules during these events. The component projects will focus on two time intervals in chick embryo limb development when major morphogenetic and differentiative events are occurring. The first period is very early in limb bud development when cell condensation and the initial differentiation into cartilage and muscle are occurring. The second is when the epiphyseal growth zones are forming. Three of the projects will deal with the regulation of molecular processes thought to be important in differentiation of cartilage and muscle, including the regulation and interrelationships of hyaluronate synthesis and cell proliferation; fibronectin and fibronectin receptor mRNA levels, gene transcription and splicing patterns; and the role of inhibitory RNA species in regulation of mRNA translation. The two other projects will study the processes involved in cartilage hypertrophy during growth plate formation, including the metabolism, supramolecular assembly and role of type X collagen which is specifically localized to hypertrophic cartilage; and the roles of collagen and interleukin-1 in controlling degradation of hypertrophic cartilage. These studies will lead to a better understanding of morphogenesis and differentiation in limb development and provide a basis for more informed investigations of genetic and teratological anomalies in limb development.